Synthesis and Preclinical Evaluation of Lu-Labeled Radiohybrid PSMA Ligands for Endoradiotherapy of Prostate Cancer.

The prostate-specific membrane antigen (PSMA)-targeted radiohybrid (rh) ligand [Lu]Lu-rhPSMA-7.3 has recently been assessed in a pretherapeutic dosimetry study on prostate cancer patients. In comparison to [Lu]Lu-PSMA I&T, application of [Lu]Lu-rhPSMA-7.

Substitution of l-Tryptophan by -Methyl-l-Tryptophan in Lu-RM2 Results in Lu-AMTG, a High-Affinity Gastrin-Releasing Peptide Receptor Ligand with Improved In Vivo Stability.

Theranostic applications targeting the gastrin-releasing peptide receptor (GRPR) have shown promising results. When compared with other peptide ligands for radioligand therapy, the most often used GRPR ligand, DOTA-Pip-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH (RM2), may be clinically impacted by limited metabolic stability. With the aim of improving the metabolic stability of RM2, we investigated whether the metabolically unstable Gln-Trp bond within the pharmacophore of RM2 can be stabilized via substitution of l-Trp by α-methyl-l-tryptophan (α-Me-l-Trp) and whether the corresponding DOTAGA analog might also be advantageous.

Small peptide-based GLP-1R ligands: an approach to reduce the kidney uptake of radiolabeled GLP-1R-targeting agents?

Aim: Elevated kidney uptake in insulinoma patients remains a major limitation of radiometallated exendin-derived ligands of the glucagon-like peptide 1 receptor (GLP-1R). Based on the previously published potent GLP-1R-activating undecapeptide 1, short-chained GLP-1R ligands were developed to investigate whether kidney uptake can be reduced by means of direct F-labeling (nuclide-based accelerated renal excretion) or the reduction of the overall ligand charge (ligand-based reduced kidney uptake).

Materials & Methods: GLP-1R ligands were prepared according to optimized standard protocols via solid-phase peptide synthesis (SPPS) or, when not practicable, via fragment coupling in solution.

Design of PSMA ligands with modifications at the inhibitor part: an approach to reduce the salivary gland uptake of radiolabeled PSMA inhibitors?

Aim: To investigate whether modifications of prostate-specific membrane antigen (PSMA)-targeted radiolabeled urea-based inhibitors could reduce salivary gland uptake and thus improve tumor-to-salivary gland ratios, several analogs of a high affinity PSMA ligand were synthesized and evaluated in in vitro and in vivo studies.

Methods: Binding motifs were synthesized 'on-resin' or, when not practicable, in solution. Peptide chain elongations were performed according to optimized standard protocols via solid-phase peptide synthesis.

Preclinical comparison of four [F, Ga]rhPSMA-7 isomers: influence of the stereoconfiguration on pharmacokinetics.

Introduction: Radiohybrid (rh) ligands, a novel class of prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals, can be labeled either with [F]fluorine via isotopic exchange or with radiometals (such as [Ga]Gallium, [Lu]Lutetium, [Ac]Actinium). Among these, [F, Ga]rhPSMA-7 has recently entered clinical assessment.

Aim: Since [F, Ga]rhPSMA-7 is composed of four stereoisomers ([F, Ga]rhPSMA-7.